非经典聚腺苷酸聚合酶介导的高效RNA聚尿苷酸化
Efficient RNA polyuridylation by noncanonical poly(A) polymerases.
作者信息
Rissland Olivia S, Mikulasova Andrea, Norbury Chris J
机构信息
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
出版信息
Mol Cell Biol. 2007 May;27(10):3612-24. doi: 10.1128/MCB.02209-06. Epub 2007 Mar 12.
Abstract
Nuclear poly(A) polymerase (PAP) polyadenylates nascent mRNAs, promoting their nuclear export, stability, and translation, while the related cytoplasmic polymerase GLD-2 activates translation of deadenylated mRNAs. Here we characterize the biochemical activity of fission yeast Schizosaccharomyces pombe Cid1, a putative cytoplasmic PAP implicated in cell cycle checkpoint controls. Surprisingly, Cid1 has robust poly(U) polymerase activity in vitro, especially when isolated in native multiprotein complexes. Furthermore, we found that upon S-phase arrest, the 3' ends of actin mRNAs were posttranscriptionally uridylated in a Cid1-dependent manner. Finally, Hs2 (ZCCHC6), a human ortholog of Cid1, shows similar activity. These data suggest that uridylation of mRNA forms the basis of an evolutionarily conserved mechanism of gene regulation.
摘要
核聚腺苷酸聚合酶（PAP）为新生mRNA加上聚腺苷酸尾，促进其核输出、稳定性及翻译，而相关的胞质聚合酶GLD-2则激活去腺苷酸化mRNA的翻译。在此，我们对粟酒裂殖酵母Cid1的生化活性进行了表征，Cid1是一种与细胞周期检查点控制有关的假定胞质PAP。令人惊讶的是，Cid1在体外具有强大的聚尿苷酸聚合酶活性，尤其是当它以天然多蛋白复合物形式分离时。此外，我们发现，在S期阻滞时，肌动蛋白mRNA的3'端以Cid1依赖的方式在转录后被尿苷酸化。最后，Cid1的人类同源物Hs2（ZCCHC6）表现出类似的活性。这些数据表明，mRNA的尿苷酸化构成了一种进化上保守的基因调控机制的基础。
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